DESCRIPTION (provided by investigator): This application addresses Challenge Area 08, "Genomics," and Challenge Topic 08-AG-105 (also OD [OBSSR] - 102), "Approaches to study the interactions among individual behaviors, social and physical environments, and genetic/epigenetic processes during critical developmental periods." Decades of animal physiology experiments unequivocally show that perturbations during early, plastic, critical periods of development can have lifelong, sometimes irreversible adverse impact on markers of chronic cardio- metabolic disease like adiposity, blood pressure and glucose intolerance, and on lifespan itself. The field of epigenetics has recently revealed some of the mechanisms underlying these observations. For example, in the yellow agouti mouse model, a maternal diet rich in methyl donors around conception causes DNA methylation of a metastable epiallele, preventing offspring from becoming fat, diabetic, and cancer-prone. No study in human populations, however, has examined pathways from maternal diet in early pregnancy through epigenetic changes to offspring phenotype. The goals of this study are to examine relationships among maternal diet in early pregnancy, particularly variation in intake of methyl donors, global DNA methylation in maternal blood in early and late pregnancy and in umbilical cord blood, and adiposity-related outcomes in 3- and 7-year-old children. We will carry out this project within the well-characterized pre-birth cohort study Project Viva, which is perhaps the only US-based epidemiologic study with the design features to address these aims: prospectively collected, validated, early pregnancy diet information, maternal and cord blood specimens, and research- quality offspring cardio-metabolic phenotype data. Obesity, cardiovascular disease, diabetes, and related conditions are leading causes of morbidity and mortality in the U.S., and their earliest origins exist in behavior and environment during the prenatal period. Adding epigenetic data to existing epidemiologic studies offers the potential to translate knowledge from animal experiments to the human condition as well as to mount preventive interventions. Given the potential scientific and public health impact, the time has come for an influx of funds to advance this area in significant ways quickly, and the Challenge Grants program provides the right vehicle to do so. PUBLIC HEALTH RELEVANCE: The goals of this study are to examine the extent to which maternal diet in early pregnancy affects methylation of maternal and fetal DNA, an epigenetic process;and the extent to which DNA methylation predicts obesity and cardiovascular risk factors in 3- and 7-year-old children. The importance of this research is two-fold. First is knowledge acquisition--the potential to translate findings from animal experiments to the human condition. Second is public health importance-- optimizing maternal diet in early pregnancy could improve the health of the next generation.